The treatment of solid-tumor cancers continues to rely on the development of architecturally new and biologically more potent and anti-tumor, antimitotic agents. Vincristine, taxol, dolastatin 10 and combretastatin A-4 (CA-4) prodrugs have established clinical efficacy as antimitotic agents. We have designed (molecular modeling and 3D-QSAR) and synthesized a novel class of compounds viz. cyclopentenone derivatives i.e 2,3-diaryl-4 or 5-substituted cyclopent-2-en-1-one derivatives in particular which could mimic combretastatin A-4. The lead compounds in our designed molecules demonstrate remarkable cytotoxic activity against a variety of human cancer cell lines representing cancer of the colon, pancreas, larynx, ovary, duodenum, kidney, oral cavity, prostate, lung, endothelial cells and leukemias